Endometrial Cancer

Question 1

What is endometrial cancer?

Answer 1

Endometrial cancer is cancer of the endometrium, the lining of the uterus.

Question 2

What is the most common type of endometrial cancer?

Answer 2

Around 80% of cases are adenocarcinoma.

Question 3

What hormone does endometrial cancer depend on?

Answer 3

t is an oestrogen-dependent cancer, meaning that oestrogenstimulates the growth of endometrial cancer cells.

Question 4

If a woman presents with postmenopausal bleeding what is the number one differential?

Answer 4

Any woman presenting with postmenopausal bleeding has endometrial cancer until proven otherwise.

Question 5

Briefly describe endometrial hyperplasia

Answer 5

Endometrial hyperplasia is a precancerous condition involving thickening of the endometrium. The risk factors, presentation and investigations of endometrial hyperplasia are similar to endometrial cancer. Most cases of endometrial hyperplasia will return to normal over time. Less than 5% go on to become endometrial cancer. There are two types of endometrial hyperplasia to be aware of:

• Hyperplasia without atypia
• Atypical hyperplasia

Question 6

Briefly describe the treatment of endometrial hyperplasia

Answer 6

Endometrial hyperplasia may be treated by a specialist using progestogens, with either:

• Intrauterine system (e.g. Mirena coil)
• Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)

Question 7

What are the risk factors for endometrial cancer?

Answer 7

Situations where there is increased exposure of unopposed oestrogen are:

• Increased age
• Earlier onset of menstruation
• Late menopause
• Oestrogen only hormone replacement therapy
• No or fewer pregnancies
• Obesity
• Polycystic ovarian syndrome
• Tamoxifen

Question 8

Why does unopposed oestrogen lead to endometrial cancer?

Answer 8

The risk factors for endometrial cancer are due to the patient’s exposure to unopposed oestrogen. Unopposed oestrogen refers to oestrogen without progesterone. Unopposed oestrogen stimulates the endometrial cells and increases the risk of endometrial hyperplasia and cancer. The risk endometrial cancer is associated with the amount of unopposed oestrogen the endometrium is exposed to during the patient’s life.

Question 9

Why do women with polycystic ovarian syndrome (PCOS) have an increased risk of endometrial cancer?

Answer 9

Polycystic ovarian syndrome leads to increased exposure to unopposed oestrogen due to a lack of ovulation. Usually, when ovulation occurs, a corpus luteum is formed in the ovaries from the ruptured follicle that released the egg. It is this corpus luteum that produces progesterone, providing endometrial protection during the luteal phase of the menstrual cycle (the second half of the menstrual cycle). Women with polycystic ovarian syndrome are less likely to ovulate and form a corpus luteum. Without developing a corpus luteum during the menstrual cycle, progesterone is not produced, and the endometrial lining has more exposure to unopposed oestrogen.

Question 10

What is offered to women with PCOS for endometrial protection?

Answer 10

For endometrial protection, women with PCOS should have one of:

• The combined contraceptive pill
• An intrauterine system (e.g. Mirena coil)
• Cyclical progestogens to induce a withdrawal bleed.

Question 11

Why do obese with have an increased risk of endometrial cancer?

Answer 11

Obesity is a crucial risk factor because adipose tissue (fat) is a source of oestrogen. Adipose tissue is the primary source of oestrogen in postmenopausal women. Adipose tissue contains aromatase, which is an enzyme that converts androgens such as testosterone into oestrogen. Androgens are produced mainly by the adrenal glands. In women with more adipose tissue, and therefore more aromatase enzyme, more of these androgens are converted to oestrogen. This extra oestrogen is unopposed in women that are not ovulating (e.g. PCOS or postmenopause), because there is no corpus luteum to produce progesterone.

Question 12

Why does tamoxifen increase the risk of endometrial cancer.

Answer 12

Tamoxifen has an anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer.

Question 13

What are the 2 additional risk factots for endometrial cancer that are not due to unopposed oestrogen?

Answer 13

Additional risk factors not related to unopposed oestrogen are:

• Type 2 diabetes
• Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome

Question 14

Why does type 2 diabetes increase the risk of endometrial cancer?

Answer 14

Type 2 diabetes may increase the risk of endometrial cancer due to the increased production of insulin. Insulin may stimulate the endometrial cells and increase the risk of endometrial hyperplasia and cancer. PCOS is also associated with insulin resistance and increased insulin production. Insulin resistance further adds to the risk of endometrial cancer in women with PCOS.

Question 15

What are the protective factors for endometrial cancer?

Answer 15

Protective factors against endometrial cancer include:

• Combined contraceptive pill
• Mirena coil
• Increased pregnancies
• Cigarette smoking

Smoking appears to be protective against endometrial cancer in postmenopausal women by being anti-oestrogenic. Interestingly, it is not protective against other oestrogen dependent cancers, such as breast cancer (where it increases the risk).

Question 16

Why may smoking be anti-oestrogenic?

Answer 16

Smoking may have anti-oestrogenic effects in several ways:

• Oestrogen may be metabolised differently in smokers
• Smokers tend to be leaner, meaning they have less adipose tissue and aromatase enzyme
• Smoking destroys oocytes (eggs), resulting in an earlier menopause

Question 17

What is the most important symptom of endometrial cancer to be aware of?

Answer 17

The number one presenting symptom of endometrial cancer to remember for your exams is postmenopausal bleeding.

Question 18

How can endometrial cancer present?

Answer 18

The number one presenting symptom of endometrial cancer to remember for your exams is postmenopausal bleeding.

Endometrial cancer may also present with:

• Postcoital bleeding
• Intermenstrual bleeding
• Unusually heavy menstrual bleeding
• Abnormal vaginal discharge
• Haematuria
• Anaemia
• Raised platelet count

Question 19

What is the referral criteria for the 2-week-wait pathway for endometrial cancer?

Answer 19

The referral criteria for a 2-week-wait urgent cancer referral for endometrial cancer is:

• Postmenopausal bleeding (more than 12 months after the last menstrual period)

Question 20

What is the NICE guidance for a transvaginal ultrasound in women over 55 years?

Answer 20

NICE also recommends referral for a transvaginal ultrasound in women over 55 years with:

• Unexplained vaginal discharge
• Visible haematuria plus raised platelets, anaemia or elevated glucose levels

Question 21

What investigations should be ordered for endometrial cancer?

Answer 21

There are three investigations to remember for diagnosing and excluding endometrial cancer:

• Transvaginal ultrasound for endometrial thickness (normal is less than 4mm post-menopause)
• Pipelle biopsy, which is highly sensitive for endometrial cancer making it useful for excluding cancer
• Hysteroscopy with endometrial biopsy

Depending on local guidelines, a normal transvaginal ultrasound (endometrial thickness < 4mm) and normal pipelle biopsy are sufficient to demonstrate a very low risk of endometrial cancer and discharge the patient.

Question 22

Briefly describe the role of a pipelle biopsy in endometrial cancer

Answer 22

A pipelle biopsy can be taken in the outpatient clinic. It involves a speculum examination and inserting a thin tube (pipelle) through the cervix into the uterus. This small tube fills with a sample of endometrial tissue that can be examined for signs of endometrial hyperplasia or cancer. Pipelle biopsy is a quicker and less invasive alternative to hysteroscopy for excluding cancer in lower-risk women.

Question 23

Briefly describe the staging criteria for endometrial cancer

Answer 23

The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage endometrial cancer:

• Stage 1: confined to the uterus
• Stage 2: invades the cervix
• Stage 3: invades the ovaries, fallopian tubes, vagina or lymph nodes
• Stage 4: invades bladder, rectum or beyond the pelvis

Question 24

Briefly describe the management of endometrial cancer

Answer 24

The usual treatment for stage 1 and 2 endometrial cancer is a total abdominal hysterectomy with bilateral salpingo-oophorectomy, also known as a TAH and BSO (removal of uterus, cervix and adnexa).

Other treatment options depending on the individual presentation include:

• A radical hysterectomy involves also removing the pelvic lymph nodes, surrounding tissues and top of the vagina
• Radiotherapy
• Chemotherapy
• Progesterone may be used as a hormonal treatment to slow the progression of the cancer